ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers

Autor: Gian Paolo Marcuzzi, N. Würdemann, Jens M. Seeger, Steffen Wagner, Anamaria Đukić, Matthias Kirschberg, Jens Peter Klussmann, Slawomir Majewski, Hamid Kashkar, Alexander Quaas, Baki Akgül, Martin Hufbauer, Vjekoslav Tomaić, Claus Wittekindt, Sandra Heuser
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
ATP5B
Science
Cell
Oxidative phosphorylation
Human papilloma virus
Alphapapillomavirus
medicine.disease_cause
Article
Oxidative Phosphorylation
human papillomaviruses (HPV)
cell metabolism
mitochondrial ATP-synthase (ATP5B)
HPV-mediated tumorigenesis
03 medical and health sciences
0302 clinical medicine
Viral life cycle
medicine
Humans
Glycolysis
Head and neck cancer
Multidisciplinary
biology
ATP synthase
Squamous Cell Carcinoma of Head and Neck
Papillomavirus Infections
virus diseases
Basic Medical Sciences
Oncogene Proteins
Viral
Mitochondrial Proton-Translocating ATPases
Survival Analysis
female genital diseases and pregnancy complications
3. Good health
Oropharyngeal Neoplasms
Tumor Virus Infections
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
biology.protein
Medicine
Female
Carcinogenesis
ATP synthase alpha/beta subunits
Protein Binding
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reports
Scientific reports
ISSN: 2045-2322
Popis: Mucosal and skin cancers are associated with infections by human papillomaviruses (HPV). The manner how viral oncoproteins hijack the host cell metabolism to meet their own energy demands and how this may contribute to tumorigenesis is poorly understood. We now show that the HPV oncoprotein E7 of HPV8, HPV11 and HPV16 directly interact with the beta subunit of the mitochondrial ATP-synthase (ATP5B), which may therefore represent a conserved feature across different HPV genera. By measuring both glycolytic and mitochondrial activity we observed that the association of E7 with ATP5B was accompanied by reduction of glycolytic activity. Interestingly, there was a drastic increase in spare mitochondrial respiratory capacity in HPV8-E7 and an even more profound increase in HPV16-E7 expressing cells. In addition, we could show that ATP5B levels were unchanged in betaHPV positive skin cancers. However, comparing HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) we noticed that, while ATP5B expression levels did not correlate with patient overall survival in HPV-negative OPSCC, there was a strong correlation within the HPV16-positive OPSCC patient group. These novel findings provide evidence that HPV targets the host cell energy metabolism important for viral life cycle and HPV-mediated tumorigenesis.
Databáze: OpenAIRE
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